PLoS pathogens, 2009-02, Vol.5 (2), p.e1000292-e1000292
2009
Details
- Autor(en) / Beteiligte
- Titel
- Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity
- Ist Teil von
- PLoS pathogens, 2009-02, Vol.5 (2), p.e1000292-e1000292
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The cytidine deaminases APOBEC3G and APOBEC3F exert anti-HIV-1 activity that is countered by the HIV-1 vif protein. Based on potential transcription factor binding sites in their putative promoters, we hypothesized that expression of APOBEC3G and APOBEC3F would vary with T helper lymphocyte differentiation. Naive CD4+ T lymphocytes were differentiated to T helper type 1 (Th1) and 2 (Th2) effector cells by expression of transcription factors Tbet and GATA3, respectively, as well as by cytokine polarization. APOBEC3G and APOBEC3F RNA levels, and APOBEC3G protein levels, were higher in Th1 than in Th2 cells. T cell receptor stimulation further increased APOBEC3G and APOBEC3F expression in Tbet- and control-transduced, but not in GATA3-transduced, cells. Neutralizing anti-interferon-gamma antibodies reduced both basal and T cell receptor-stimulated APOBEC3G and APOBEC3F expression in Tbet- and control-transduced cells. HIV-1 produced from Th1 cells had more virion APOBEC3G, and decreased infectivity, compared to virions produced from Th2 cells. These differences between Th1- and Th2-produced virions were greater for viruses lacking functional vif, but also seen with vif-positive viruses. Over-expression of APOBEC3G in Th2 cells decreased the infectivity of virions produced from Th2 cells, and reduction of APOBEC3G in Th1 cells increased infectivity of virions produced from Th1 cells, consistent with a causal role for APOBEC3G in the infectivity difference. These results indicate that APOBEC3G and APOBEC3F levels vary physiologically during CD4+ T lymphocyte differentiation, that interferon-gamma contributes to this modulation, and that this physiological regulation can cause changes in infectivity of progeny virions, even in the presence of HIV-1 vif.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1000292Titel-ID: cdi_plos_journals_1289063574
- Format
- –
- Schlagworte
- Acquired immune deficiency syndrome, AIDS, Aminotransferases, APOBEC-3G Deaminase, CD4 lymphocytes, Cytidine Deaminase - genetics, Cytidine Deaminase - metabolism, Cytosine Deaminase - genetics, Cytosine Deaminase - metabolism, Development and progression, Flow Cytometry, GATA3 Transcription Factor - metabolism, Gene Expression Regulation, Genetic aspects, HIV, HIV infection, HIV-1 - physiology, Human immunodeficiency virus, Humans, Immunology/Cellular Microbiology and Pathogenesis, Immunology/Leukocyte Signaling and Gene Expression, Infectious Diseases/HIV Infection and AIDS, Interferon-gamma - metabolism, Lymphocytes, Microbiology/Cellular Microbiology and Pathogenesis, Microbiology/Innate Immunity, Physiological aspects, Proteins, T cell receptors, Th1 Cells - immunology, Th1 Cells - metabolism, Th1 Cells - virology, Th2 Cells - immunology, Th2 Cells - metabolism, Th2 Cells - virology, Transcription Factors - metabolism, vif Gene Products, Human Immunodeficiency Virus - metabolism, Virion - metabolism, Virology/Host Antiviral Responses, Virology/Immunodeficiency Viruses, Virology/Mechanisms of Resistance and Susceptibility, including Host Genetics, Virology/Virulence Factors and Mechanisms